Effects of Mn concentration on the ac magnetically induced heating characteristics of superparamagnetic MnxZn1−xFe2O4 nanoparticles for hyperthermia

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Effects of Mn concentration on the ac magnetically induced heating

characteristics of superparamagnetic MnxZn1−xFe2O4 nanoparticles for hyperthermia

Minhong Jeun, Seung Je Moon, Hiroki Kobayashi, Hye Young Shin, Asahi Tomitaka et al.

Citation: Appl. Phys. Lett. 96, 202511 (2010); doi: 10.1063/1.3430043 View online: http://dx.doi.org/10.1063/1.3430043

View Table of Contents: http://apl.aip.org/resource/1/APPLAB/v96/i20 Published by the American Institute of Physics.

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Effects of Mn concentration on the ac magnetically induced heating characteristics of superparamagnetic Mn

_x

Zn

_1−x

Fe

₂

O

₄

nanoparticles for hyperthermia

Minhong Jeun,¹Seung Je Moon,¹Hiroki Kobayashi,²Hye Young Shin,³Asahi Tomitaka,² Yu Jeong Kim,⁴Yasushi Takemura,²Sun Ha Paek,³Ki Ho Park,⁴Kyung-Won Chung,⁵ and Seongtae Bae^1,a^兲

1Department of Electrical and Computer Engineering, Biomagnetics Laboratory (BML), National University of Singapore, Singapore 117576

2Department of Electrical and Computer Engineering, Yokohama National University, Yokohama 240-8501, Japan

3Department of Neurosurgery, Cancer Research Institute, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

4Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

5Daion Co. Ltd., Incheon 405-846, Republic of Korea

共Received 8 February 2010; accepted 25 April 2010; published online 21 May 2010兲

The effects of Mn²⁺cation concentration on the ac magnetically induced heating characteristics and the magnetic properties of superparamagnetic Mn_xZn_1−xFe₂O₄ nanoparticles 共SPNPs兲 were investigated to explore the biotechnical feasibility as a hyperthermia agent. Among the Mn_xZn_1−xFe₂O₄ SPNPs, the Mn_0.5Zn_0.5Fe₂O₄ SPNP showed the highest ac magnetically induced heating temperature 共⌬Tac,mag兲, the highest specific absorption rate 共SAR兲, and the highest biocompatibility. The higher out of phase susceptibility共␹m⬙兲value and the higher chemical stability systematically controlled by the replacement of Zn²⁺ cations by the Mn²⁺ cations on the A-site 共tetrahedral site兲 are the primary physical reason for the promising biotechnical properties of Mn_0.5Zn_0.5Fe₂O₄ SPNP. ©2010 American Institute of Physics.关doi:10.1063/1.3430043兴

Magnetic hyperthermia共MH兲using a superparamagntice nanoparticle agent 共SPNA兲has recently drawn huge attrac- tion due to its clinical promises.^1,2Accordingly, the interests to utilize the ternary phase of SPNPs, MFe₂O₄共M = Fe, Co, Ni, and Mg兲, with a mean diameter below 10 nm for a MH agent has increased dramatically. However, despite their promising chemical, physiological, biotechnical, and physical properties suitable for SPNA applications,³an insufficient

⌬T_ac,magand low specific absorption rate共SAR兲at the physi- ologically tolerable range of frequencies and magnetic fields 共fappl⬍100 kHz, H_appl⬍200 Oe兲 are still revealed as the technical challenges to be overcome for a real clinical MH.^4,5 Thus, a great deal of research activity is being conducted in order to develop a functional SPNA and to improve the effi- ciency of currently used ferrite SPNAs. The quarterly phase of bulk Mn_xZn_1−xFe₂O₄, which is one of the softest 共or the highest permeability兲 ferrite materials, is considered to be a potential material for MH agent. The main physical reason is that it has a good electrical field absorption and a large power loss共500– 200 W/m³兲at a low frequency 共⬍100 kHz兲 which is due to its low electrical resistivity 共0.02– 20 ⍀m兲.^6,7Furthermore, its magnetic properties, i.e., saturation magnetization, M_s, and magnetic susceptibility 共␹m=␹m⬘⁺ⁱ␹m⬙, particularly ␹m⬙兲, which are directly relevant to the ⌬Tac,mag characteristics, can be easily controlled by adjusting the relative concentration of Mn²⁺and Zn²⁺cations in the Mn_xZn_1−xFe₂O₄.^6,8,9 However, all of the works relevant to the Mn_xZn_1−xFe₂O₄ done so far were entirely fo-

cused on magnetoelectronics device applications.¹⁰ There have been no systematic studies on the magnetic properties,

⌬Tac,mag characteristics, and the biocompatibility of Mn_xZn_1−xFe₂O₄SPNPs for MH agent applications until now.

In this paper, we report on the effects of Mn²⁺ cation concentration on the magnetic properties and the ⌬Tac,mag

characteristics of Mn_xZn_1−xFe₂O₄ SPNPs to explore its feasibility as a MH agent. The physical correlation between the magnetic properties of Mn_xZn_1−xFe₂O₄SPNPs controlled by the Mn²⁺ cation concentration and ⌬T_ac,mag, characteristics including power loss mechanism were systematically investigated at different ac H_appl and f_appl. In addition, the cell viability of Mn_xZn_1−xFe₂O₄ SPNPs with different Mn²⁺cation concentrations were quantitatively analyzed to evaluate the biocompatibility forin vivoMH agent applications.

The spinel ferrite Mn_xZn_1−xFe₂O₄ nanoparticles 共NPs兲 with different Mn²⁺ cation concentration were synthesized using a modified high temperature thermal decomposition 共HTTD兲 method, where ramping up rate and heat treatment time were changed to 8.5 ° C/min and 25 min, respectively, compared to a conventional HTTD method.¹¹The Mn²⁺cation concentration of Mn_xZn_1−xFe₂O₄NPs was systematically controlled from x = 0.2 to 0.8 during the synthesis. The crystal structure, the particle size, and the distribution of Mn_xZn_1−xFe₂O₄ NPs were analyzed by using a Cu-k␣radi- ated x-ray diffractometer共XRD兲and a high resolution trans- mission electron microscopy 共HRTEM兲. The ⌬Tac,mag characteristics and the ac magnetic hysteresis of the solid state Mn_xZn_1−xFe₂O₄NPs were measured by using an ac solenoid coil system, which is connected to a capacitor. The f_appland the H_applwere varied from 30 kHz to 210 kHz and from 60 Oe to 140 Oe, respectively. The dc magnetic properties of the

a兲Author to whom correspondence should be addressed. Electronic mail:

[email protected].

APPLIED PHYSICS LETTERS96, 202511共2010兲

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solid state Mn_xZn_1−xFe₂O₄ NPs were analyzed by using a vibrating sample magnetometer and the ac␹mwas measured by using an ac magnetosusceptometer. The zero field cooling/field cooling共ZFC/FC兲measurement was carried out to characterize the dependence of temperature on the magnetic properties of Mn_xZn_1−xFe₂O₄ NPs using a supercon- ducting quantum interference device 共SQUID兲. The cell viability was quantitatively analyzed by employing the methylthiazol tetrazolium bromide test 共MTT兲 using neuronal stem cells 共NSCs兲isolated from human fetal midbrain. The Mn_xZn_1−xFe₂O₄ NPs were dispersed into the mixed media of 2.5% alcohol, Dulbeco’s modified eagle’s medium, 10% fetal bovine serum, 1% penicillin streptomy- cin, and 2 mM glutamine. The concentration of Mn_xZn_1−xFe₂O₄ NPs in the media were varied from 5 to 25 ␮g/ml.

Prior to studying the magnetic properties and the

⌬Tac,magcharacteristics, the crystal structure, the particle size and the distribution of Mn_xZn_1−xFe₂O₄NPs were first investigated. As can be seen in Fig. 1, all of the Mn_xZn_1−xFe₂O₄ NPs had a mean particle size of 5.7–6 nm with a 12% standard deviation and they were well segregated with a round shapes. In addition, the Mn_xZn_1−xFe₂O₄NPs showed a single phase cubic spinel ferrite structure and did not exhibit any undesirable crystalline phases. The well controlled structural and chemical stabilities of Mn_xZn_1−xFe₂O₄NPs demonstrate that they can be considered to be an in vivo MH agent be- cause they are expected to minimize the biochemical reac- tion with chemical components in the blood stream and to allow for stable intravenous circulation.

Figure 2 shows the hysteresis loops of Mn_xZn_1−xFe₂O₄ NPs measured under an externally applied field of 共a兲

=⫾10 kOe and共b兲 =⫾80 Oe at room temperature. All of the Mn_xZn_1−xFe₂O₄ NPs had superparamagnetic 共SP兲 properties. Furthermore, the ZFC/FC measurement results 共not shown in this paper兲confirmed that the blocking temperature of Mn_xZn_1−xFe₂O₄NPs is in the range of 80–120 K depend- ing on the Mn²⁺ cation concentration, indicating that they have a SP phase at room temperature. As shown in Fig.2共a兲, the M_shad a strong dependence on the Mn²⁺cation concen-

tration. Particularly, the Mn_0.5Zn_0.5Fe₂O₄ NPs had the highest M_svalue of a 47 emu/g. The increase in M_sby increasing the Mn²⁺ cation concentration up to x = 0.5 is thought to be due to the increase in magnetic moment of the unit cell up to 7.5 ␮B 共␮B: Bohr magneton兲 which resulted from the replacement of Zn²⁺ions by Mn²⁺ions on theA-site. However, increasing the Mn²⁺ cation concentration above x = 0.5 was found to decrease the M_s. This decrease in M_s is due to the development of antiferromagnetic alignment of Fe³⁺ions on the B-site关see Fig.3共c兲兴.⁶

Figure3 shows the dependence of Mn²⁺ cation concentration on the ⌬Tac,mag and the magnetic properties of Mn_xZn_1−xFe₂O₄ SPNPs. In Fig. 3共a兲, it can be clearly ob- served that the ⌬T_ac,mag measured at a constant H_appl

= 80 Oe, f_appl= 210 kHz had a strong dependence on the Mn²⁺ cation concentration. The ⌬Tac,mag of Mn_xZn_1−xFe₂O₄SPNPs was increased by increasing the Mn concentration and reached a maximum ⌬Tac,mag= 39 ° C at the composition of Mn_0.5Zn_0.5Fe₂O₄. A further increase in Mn concentration, x⬎0.5, led to a severe reduction in

⌬Tac,mag. The physical dependence of f_appl andH_appl on the

⌬Tac,mag is shown in Fig.3共b兲. It was clearly demonstrated that the ⌬T_ac,mag is linearly proportional to the f_appl and squarely proportional to theH_appl. These results strongly im- ply that the physical nature of ⌬Tac,mag of Mn_xZn_1−xFe₂O₄

FIG. 1. HRTEM images and XRD patterns of synthesized superparamagnetic Mn_xZn_1−xFe₂O₄nanoparticles with different Mn composition: 共a兲x

= 0.33,共b兲x = 0.5,共c兲x = 0.67, and共d兲XRD patterns.

FIG. 2. Magnetic hysteresis loops of Mn_xZn_1−xFe₂O₄ nanoparticles with different Mn²⁺cation concentration changed from x = 0.2 to 0.8.共a兲Major loop and共b兲minor loop.

FIG. 3. Dependence of Mn²⁺cation concentration on the共a兲ac magnetically induced heating characteristics measured at the fixed H_appl= 80 Oe and f_appl= 210 kHz, 共b兲 applied frequency and magnetic field, and共c兲 SAR, heating power共total and relaxation loss兲, magnetization, out of phase susceptibility and ac magnetic coercivity of superparamagnetic Mn_xZn_1−xFe₂O₄ nanoparticles关䊐SAR,䊏magnetization共dc兲,䊊P_total,쎲Prelaxation loss,䉭ac susceptibility, and䉱coercivity共ac兲兴.

202511-2 Jeunet al. Appl. Phys. Lett.96, 202511共2010兲

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SPNPs is dominantly related to the “relaxation loss” heating power,Prelaxation loss, as described in Eqs.共1兲and共2兲.¹² Fur- thermore, from this point of view, the highest⌬Tac,magvalue obtained from the Mn_0.5Zn_0.5Fe₂O₄SPNP can be understood to be due to its highest measured ␹_m⬙ value which resulted from its softest magnetic property as well as its largest ex- change energy induced by the half portion of Zn²⁺ ions re- placed by the Mn²⁺ ions on theA-site.

Prelaxation loss=␲␮0␹m

储f_applH_appl² , 共1兲

␹^储⁼␹0

2␲^f␶ 1 +共2␲^f␶兲²,1

␶⁼ 1

␶N

+ 1

␶B

⬇ 1

␶N

= 2

冑

KuV/kBT

冑

_␲·␶0exp共KuV/kBT兲,共soft ferrite:␶NⰆ␶B兲, 共2兲 where␶N: Néel relaxation time,␶B: Brownian relaxation time, ␶0:relaxation factor, andKu: magnetic anisotropy.

The ac magnetic coercivity of Mn_xZn_1−xFe₂O₄ SPNPs measured atH_appl=⫾80 Oe and f_appl= 210 kHz is shown in Fig.3共c兲. The Mn0.5Zn_0.5Fe₂O₄SPNP exhibited the smallest ac magnetic coercivity among the Mn_xZn_1−xFe₂O₄ SPNPs indicating that it has the lowest ac magnetic anisotropy re- sulting in the fastest ␶N关or the highest␹m⬙ described in Eq.

共2兲兴. This experimental result provides strong physical evi- dence that the highest ⌬T_ac,mag of Mn_0.5Zn_0.5Fe₂O₄ SPNP 共x = 0.5兲is related directly to the well-controlled highest␹m⬙^. Furthermore, this indicates that controlling the ac magnetic softness of SPNPs, which is directly relevant to the Néel relaxation behavior, is the most crucial factor in determining the ⌬Tac,mag characteristics. In order to further clarify the physical mechanism of⌬Tac,mag of Mn_xZn_1−xFe₂O₄ SPNPs, the contribution of Prelaxation lossto the total power heat gen- eration,P_total, was numerically compared by calculating both P_total and Prelaxation loss from the experimentally obtained

⌬Tac,mag, ␹m⬙ 共at f_appl= 210 kHz兲, mass, and the volumetric heat capacity values of Mn_xZn_1−xFe₂O₄ SPNPs. As can be seen in Fig. 3共c兲, more than 80% or 90% of Prelaxation loss

contributed to the P_totalof Mn_xZn_1−xFe₂O₄ SPNPs verifying that the Prelaxation loss, particularly the Néel relaxation power loss is dominant for the⌬Tac,magof Mn_xZn_1−xFe₂O₄SPNPs.

To consider the SPNPs for a real clinical MH agent without systemic side effect, the SPNPs should generate a higher

⌬T_ac,mag both in a short heat up time and with a amount as low as possible. These characteristics can be evaluated by the SAR shown in Fig. 3共c兲.¹³ The Mn_0.5Zn_0.5Fe₂O₄ SPNP showed the largest SAR value of 138.4 W/g due to the fastest temperature rising rate 共⌬T/⌬t兲 caused by the highest ␹⬙ value among the Mn_xZn_1−xFe₂O₄SPNPs. This value is considered to be much higher than those obtained from the conventional ternary phase SPNAs at the same ac condition, e.g., Fe₃O₄ 共27.3 W/g兲, CoFe2O₄ 共56.1 W/g兲, and NiFe2O₄ 共12.6 W/g兲.¹⁴

The cell viability of Mn_xZn_1−xFe₂O₄SPNPs with different concentrations was quantitatively estimated to explore the feasibility to a MH agent particularly targeted for brain tumors. Figure4showed the cell survival rate treated for共a兲 one day and共b兲two weeks, respectively. It was clearly confirmed that the cell survival rate of Mn_xZn_1−xFe₂O₄ SPNPs

depends on the concentration of NPs in the cell culture media as well as the Mn²⁺ cation concentration. All three SP- NPs showed midcytotoxicity or noncytotoxicity. In particu- lar, the Mn_0.5Zn_0.5Fe₂O₄ SPNP had the highest cell survival rate of 80%⫾8% 共10% of standard deviation兲 even at a higher NP concentration and for a long treatment time. The higher cell survival rate of Mn_0.5Zn_0.5Fe₂O₄SPNP is thought to be due to the chemically stable phase of Mn_0.5Zn_0.5Fe₂O₄, which is expected to induce less stress on the cells and the large portion of Mn²⁺cation concentration, which is considered to have a high biocompatibility.¹⁵

In conclusion, it was demonstrated that the⌬Tac,magand the magnetic properties of Mn_xZn_1−xFe₂O₄ SPNPs had a strong dependence on the Mn²⁺cation concentration. Among the Mn_xZn_1−xFe₂O₄ SPNPs, the Mn_0.5Zn_0.5Fe₂O₄ SPNP showed the highest ⌬Tac,mag, SAR, and biocompatibility, which make it suitable for MH agent applications. The higher ␹⬙ value directly relevant to the ␶N共or ac magnetic softness兲 and the higher chemical stability systematically controlled by the replacement of Zn²⁺ cations by the Mn²⁺

cations on the A-site are the primary physical reason for the biotechnical promises of Mn_0.5Zn_0.5Fe₂O₄ SPNP.

1P. Moroz, S. K. Jones, and B. N. Gray, Int. J. Hyperthermia 18, 267 共2002兲.

2Q. A. Pankhurst, N. K. T. Thanh, S. K. Jones, and J. Dobson,J. Phys. D:

Appl. Phys. 42, 224001共2009兲.

3S. Bae, S. W. Lee, and Y. Takemura,Appl. Phys. Lett.89, 252503共2006兲.

4P. Wust, U. Gneveckow, U. M. Johannsen, D. Böhmer, T. Henkel, F.

Kahmann, J. Sehouli, R. Felix, J. Ricke, and A. Jordan,Int. J. Hyperther- mia 22, 673共2006兲.

5K. Okawa, M. Sekine, M. Maeda, M. Tada, and M. Abe,J. Appl. Phys.

99, 08H102共2006兲.

6A. Goldman,Modern Ferrite Technology共Springer, New York, 2006兲.

7M. Sugimoto, J. Am. Ceram. Soc. 82, 269-80共1999兲.

8R. E. Rosensweig,J. Magn. Magn. Mater. 252, 370共2002兲.

9Y. Xuan, Q. Li, and G. Yang,J. Magn. Magn. Mater. 312, 464共2007兲.

10C. Rath, K. K. Sahu, S. Anand, S. K. Date, N. C. Mishra, and R. P. Das, J. Magn. Magn. Mater. 202, 77共1999兲.

11S. Sun, H. Zeng, D. B. Robinson, S. Raoux, P. M. Rice, S. X. Wang, and G. Li,J. Am. Chem. Soc. 126, 273共2004兲.

12M. Gonzales and K. M. Krishnan, J. Magn. Magn. Mater. 293, 265 共2005兲.

13T. Hosono, H. Takahashi, A. Fujita, R. J. Joseyphus, K. Tohji, and B.

Jeyadevan,J. Magn. Magn. Mater. 321, 3019共2009兲.

14S. W. Lee, S. Bae, M. Jeun, T. Koshi, and Y. Takemura, 53rd Annual Conference on Magnetism and Magnetic Materials, Texas, CG-14, 2008.

15E. John,An A-Z Guide to the Elements共Oxford University Press, Oxford, 2001兲.

FIG. 4. Cell viability of superparamagnetic Mn_xZn_1−xFe₂O₄nanoparticles 共x = 0.33, 0.5, and 0.67兲in MTT assay with NSCs isolated from human fetal midbrain treated for共a兲one day and共b兲two weeks.

202511-3 Jeunet al. Appl. Phys. Lett.96, 202511共2010兲